To understand processes underlying the performance of complex movements, we are studying sequential movements of differing length. In a study with PET we determined that premotor cortex was most related to increasing length of the sequence. With EEG, greater increases in coherence between central and frontal regions were detected for more complex finger movements. To understand motor learning, we have studied the role of sensorimotor areas in the acquisition of implicit and explicit knowledge in a sequential reaction time task using EEG. There was maximal desynchronization of the alpha activity over the contralateral sensorimotor area at the time of development of full explicit knowledge. Using functional MRI (fMRI), we studied the participation of supplementary motor area (SMA), and anterior cingulate cortex (ACC) in self-paced versus externally-triggered motor actions during sequential movements. Performance of simple sequential distal movements activates the SMA and ACC, with a larger change of signal intensity in self-paced than in triggered movements. In blind people, during Braille reading, activation has been found in the primary occipital area using both PET and fMRI. This indicates remarkable cortical plasticity. Patients with Parkinson's disease scale their movements so that they always produce a movement smaller than desired. Studies demonstrated that this might be due to an impairment in kinesthesia. Research efforts have focussed on the role of sensory feedback in the control of movements in patients with cerebellar degenerations. A multiinput-multioutput feedback control system is capable of modelling the response of the standing human body to impulsive perturbations applied to the back. The ability of patients with cerebellar degeneration to perceive differences in kinesthetic stimuli was found to be defective in tasks that were entirely passive. Studies using a task requiring multijoint coordination have been completed which suggest that deficits in motor performance in cerebellar patients is largely due to prolonged reaction times. A clinical rating scale for ataxia has been developed which correlates with the degree of cerebellar abnormality on anatomic and magnetic resonance spectroscopic imaging. We studied patients with hereditary hyperekplexia to see if reflexes thought to be mediated by glycine were affected. Reflex pathways thought to be mediated by glycinergic Ia interneurons were abnormal, but not Renshaw cells, suggesting possible compensatory changes. Two reflex pathways thought to be mediated by GABA were normal.